Limited effects of frequent CYP2D636-10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population

Purpose Although CYP2D6*36 was thought to be one of the alleles causing the poor metabolizer phenotype, several in vitro studies clarified that the enzyme produced by CYP2D6*36 showed enzymatic activities. However, the effects of CYP2D6*36 in tandem with CYP2D6*10 on the in vivo CYP2D6 activity have...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2010-10, Vol.66 (10), p.1065-1068
Main Authors: Kiyotani, Kazuma, Shimizu, Makiko, Kumai, Toshio, Kamataki, Tetsuya, Kobayashi, Shinichi, Yamazaki, Hiroshi
Format: Article
Language:English
Subjects:
Adult
Allelic copy number
Asian Continental Ancestry Group - genetics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Copy number variation
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P-450 CYP2D6 - metabolism
Dextromethorphan - metabolism
Enzymes
Excitatory Amino Acid Antagonists - metabolism
Gene Frequency
Genotype
Humans
Japan
Japanese
Male
Medical sciences
Metabolism
P450 2D6
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Phenotype
Population genetics
Reference Values
Short Communication
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Summary:Purpose Although CYP2D6*36 was thought to be one of the alleles causing the poor metabolizer phenotype, several in vitro studies clarified that the enzyme produced by CYP2D6*36 showed enzymatic activities. However, the effects of CYP2D6*36 in tandem with CYP2D6*10 on the in vivo CYP2D6 activity have been unclear. In this study, we investigated in vivo metabolic capacities of CYP2D6 among the subjects carrying different numbers of CYP2D6*36 in tandem with CYP2D6*10. Methods We measured the metabolic ratio (MR) of dextromethorphan in 98 subjects. We determined the CYP2D6 genotype of these subjects, including allelic copy number of CYP2D6*10 and CYP2D6*36 by direct sequencing, TaqMan assay, and real-time Invader assay. Results Single copies of CYP2D6*10 and tandem duplication of CYP2D6*36-*10 alleles were found at frequencies of 8.7 and 32.7%, respectively. Median dextromethorphan MRs of the subjects carrying CYP2D6*10 and CYP2D6*36-*10 were not significantly different (P = 0.24). Conclusions CYP2D6*36 in tandem with CYP2D6*10 plays a minor role in interindividual variation of dextromethorphan metabolism in vivo.
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-010-0876-4